crossing96/oncoscreening huggingface dataset:
Intracellular Propionibacterium acnes infection in glandular epithelium and stromal macrophages of the prostate with or without cancer.	BACKGROUND: Recent reports on Propionibacterium acnes (P. acnes) suggest that this bacterium is prevalent in the prostate, is associated with acute and chronic prostatic inflammation, and might have a role in prostate carcinogenesis. METHODS: To evaluate the pathogenic role of this indigenous bacterium, we screened for the bacterium in radical prostatectomy specimens using enzyme immunohistochemistry with a novel P. acnes-specific monoclonal antibody (PAL antibody), together with an anti-nuclear factor-kappa B (NF-κB) antibody. We examined formalin-fixed and paraffin-embedded tissue sections of radical prostatectomy specimens from 28 patients with prostate cancer and 18 age-matched control patients with bladder cancer, but without prostate cancer. RESULTS: Immunohistochemistry with the PAL antibody revealed small round bodies within some non-cancerous glandular epithelium and stromal macrophages in most prostate samples. Prostate cancer samples had higher frequencies of either cytoplasmic P. acnes or nuclear NF-κB expression of glandular epithelium and higher numbers of stromal macrophages with P. acnes than control samples. These parameters were also higher in the peripheral zone than in the transitional zone of the prostate, especially in prostate cancer samples. Nuclear NF-κB expression was more frequent in glands with P. acnes than in glands without P. acnes. The number of stromal macrophages with the bacterium correlated with the grade of chronic inflammation in both the PZ and TZ areas and with the grade of acute inflammation in the TZ area. CONCLUSIONS: Immunohistochemical analysis with a novel monoclonal antibody for detecting P. acnes in the prostate suggested that intraepithelial P. acnes infection in non-cancerous prostate glands and inflammation caused by the bacterium may contribute to the development of prostate cancer.	bladder
Prognostic significance of lymphovascular invasion in radical cystectomy on patients with bladder cancer: a systematic review and meta-analysis.	PURPOSE: The objective of the present study was to conduct a systematic review and meta-analysis of published literature to appraise the prognostic value of lymphovascular invasion (LVI) in radical cystectomy specimens. MATERIALS AND METHODS: Following the PRISMA statement, PubMed, Cochrane Library, and SCOPUS database were searched from the respective dates of inception until June 2013. RESULTS: A total of 21 articles met the eligibility criteria for this systematic review, which included a total of 12,527 patients ranging from 57 to 4,257 per study. LVI was detected in 34.6% in radical cystectomy specimens. LVI was associated with higher pathological T stage and tumor grade, as well as lymph node metastasis. The pooled hazard ratio (HR) was statistically significant for recurrence-free survival (pooled HR, 1.61; 95% confidence interval [CI], 1.26-2.06), cancer-specific survival (pooled HR, 1.67; 95% CI, 1.38-2.01), and overall survival (pooled HR, 1.67; 95% CI, 1.38-2.01), despite the heterogeneity among included studies. On sensitivity analysis, the pooled HRs and 95% CIs were not significantly altered when any one study was omitted. The funnel plot for overall survival demonstrated a certain degree of asymmetry, which showed slight publication bias. CONCLUSIONS: This meta-analysis indicates that LVI is significantly associated with poor outcome in patients with bladder cancer who underwent radical cystectomy. Adequately designed prospective studies are required to provide the precise prognostic significance of LVI in bladder cancer.	bladder
CXCL5 knockdown expression inhibits human bladder cancer T24 cells proliferation and migration.	CXCL5 (epithelial neutrophil activating peptide-78) which acts as a potent chemoattractant and activator of neutrophil function was reported to play a multifaceted role in tumorigenesis. To investigate the role of CXCL5 in bladder cancer progression, we examined the CXCL5 expression in bladder cancer tissues by real-time PCR and Western blot, additionally, we used shRNA-mediated silencing to generate stable CXCL5 silenced bladder cancer T24 cells and defined its biological functions. Our results demonstrated that mRNA and protein of CXCL5 is increased in human bladder tumor tissues and cell lines, down-regulation of CXCL5 in T24 cells resulted in significantly decreased cell proliferation, migration and increased cell apoptosis in vitro through Snail, PI3K-AKT and ERK1/2 signaling pathways. These data suggest that CXCL5 is critical for bladder tumor growth and progression, it may represent a potential application in cancer diagnosis and therapy.	bladder
Plasmacytoid bladder cancer: variant histology with aggressive behavior and a new mode of invasion along fascial planes.	OBJECTIVE: To examine differences in disease progression and nature of tumor invasion that may lead to more accurate expectations of tumor behavior and improved management options for plasmacytoid variant (PCV) histology urothelial bladder cancer patients. METHODS: Using the Indiana University Bladder Cancer Database, we conducted a retrospective analysis of patients undergoing radical cystectomy from 2008 to June 2013 to identify patients with PCV, micropapillary variant (MPV), or nonvariant (NV) histology and either positive ureteral margins (+UM), paravesical surgical margins (+PSM), or lymph node (+LN) involvement. Pearson's chi-squared test and analysis of variance were used for descriptive analysis. RESULTS: Of 510 patients who met inclusion criteria, 30 had +UM on final pathology. The incidence of +UM in NV patients was 17 of 457 (3.7%), in MPV 5 of 28 (17.9%), and in PCV 8 of 25 (32.0%) (P <.001). Carcinoma in situ on the luminal margin was noted for all cases, except in 5 of the 8 PCV patients with +UM, in whom retrograde longitudinal invasion along the subserosal and adventitia was noted. +PSM and +LN were significantly higher for both PCV (28.0%, 72.0%) and MPV (10.7%, 64.3%) than NV (2.6%, 18.6%, P <.001, each). CONCLUSION: PCV exhibits a unique pattern of spread along the ureter. This proposes a new mode of invasion along the fascial sheath. The incidence of +PSM and +LN liken PCV to the known aggressive MPV, and in conjunction with the increased incidence of +UM, may lead to a paradigm shift, with surgeons and pathologists being more vigilant with surgical margins.	bladder
Clinical utility of urinary soluble Fas in screening for bladder cancer.	AIM: Early diagnosis of carcinoma of urinary bladder remains a challenge. Urine cytology, as an adjunct to cystoscopy, is less sensitive for low-grade tumors. Soluble Fas (sFas), a cell-surface receptor and member of the tumor necrosis factor superfamily, is frequently expressed in urinary bladder carcinoma. The objective of this study was to investigate the urinary sFas for diagnosis of transitional cell carcinoma (TCC) of urinary bladder. METHODS: We examined urinary sFas concentration in 74 controls and 117 cases of TCC, both primary and recurrent disease, by using enzyme-linked immunosorbent assay and compared it with urinary cytology. RESULT: Urinary sFas concentration was found to be significantly higher in the patient as compared to control group (P < 0.05). An optimal cutoff value of 174.0 pg/mL was proposed. The urinary sFas level was found to have an approximate sensitivity and specificity of 88.03% and 89.19% (P < 0.001), whereas urine cytology had sensitivity of 66.67% and specificity of 95.95%. sFas had better sensitivity in higher grade and both primary and recurrent cases of urinary bladder cancer in comparison with cytology. Out of 15 node positive bladder cancer cases, 13 had high urinary sFas levels, whereas 12 were urinary cytology positive for malignancy. CONCLUSION: Urinary sFas can be used as a non-invasive diagnostic biomarker for TCC of urinary bladder, both for primary and recurrent disease.	bladder
Characterization of uptake and internalization of exosomes by bladder cancer cells.	Bladder tumors represent a special therapeutic challenge as they have a high recurrence rate requiring repeated interventions and may progress to invasive or metastatic disease. Exosomes carry proteins implicated in bladder cancer progression and have been implicated in bladder cancer cell survival. Here, we characterized exosome uptake and internalization by human bladder cancer cells using Amnis ImageStreamX, an image cytometer. Exosomes were isolated by ultracentrifugation from bladder cancer culture conditioned supernatant, labeled with PKH-26, and analyzed on the ImageStreamX with an internal standard added to determine concentration. Exosomes were cocultured with bladder cancer cells and analyzed for internalization. Using the IDEAS software, we determined exosome uptake based on the number of PKH-26+ spots and overall PKH-26 fluorescence intensity. Using unlabeled beads of a known concentration and size, we were able to determine concentrations of exosomes isolated from bladder cancer cells. We measured exosome uptake by recipient bladder cancer cells, and we demonstrated that uptake is dose and time dependent. Finally, we found that uptake is active and specific, which can be partially blocked by heparin treatment. The characterization of cellular uptake and internalization by bladder cancer cells may shed light on the role of exosomes on bladder cancer recurrence and progression.	bladder
Expression of HMGA2 in bladder cancer and its association with epithelial-to-mesenchymal transition.	OBJECTIVES: High mobility group protein2 (HMGA2) and epithelial-to-mesenchymal transition are both related to progress of bladder cancer, however, the relationship between HMGA2, E-cadherin and vimentin in bladder cancer is not yet known. Thus, this study has examined expression of HMGA2, E-cadherin and vimentin in bladder cancer and investigated their relationship. MATERIALS AND METHODS: The 5637 bladder cancer cell line and SV-HUC-1 normal uroepithelial cells were used to study expression of HMGA2, E-cadherin and vimentin using RT-PCR and western blotting. Paraffin wax-embedded bladder cancer tissues were used to study protein expression using immunohistochemistry and χ(2) analysis and Kendall's correlation were utilized statistical methods. RESULTS: Overexpression of HMGA2 was associated with down-regulation of E-cadherin and up-regulation of vimentin in the 5637 bladder cancer line. A total of 49 paraffin wax-embedded tissues of transitional cell bladder cancer were used. Positive expression levels of HMGA2 protein and vimentin were 41 and 43% in bladder tissues, respectively. No expression of E-cadherin was found in 43%. Expression of HMGA2, loss of E-cadherin and expression of vimentin are all significantly correlated with bladder cancer grade and stage. Loss of E-cadherin and expression of vimentin both correlated with recurrence of the bladder cancer. CONCLUSIONS: Expression of HMGA2 was closely associated with occurrence of epithelial-to-mesenchymal transition. Expression of HMGA2, loss of E-cadherin and expression of vimentin may indicate high degree malignancy of bladder cancer. Loss of E-cadherin expression and positive expression of vimentin may predict recurrence of bladder cancer.	bladder
Computed tomography or magnetic resonance imaging - our experiences in determining preoperative TNM staging of bladder cancer.	Bladder cancer is the ninth most common cancer diagnosis worldwide. Early detection of bladder cancer is important, since up to 47% of bladder cancer-related deaths might be avoided. AIM: To show our experience in determining the staging of bladder cancer with multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI), making comparison of stage accuracy with contrast enhanced MDCT, conventional MR imaging and dynamic contrast-enhanced MR imaging on the one hand and pathoistological diagnoses after transurethral resection of the non-muscle invasive bladder cancers or radical cystectomy for patients with muscle-invasive bladder cancers. MATERIALS AND METHODS: Ninety patients with histologically proved bladder cancer were prospectively examined with MDCT, conventional and dynamic MR imaging before tumour resection. RESULTS: Staging was correct in 55.6% with CT, 56.7% with conventional MRI and in 86.7% with dynamic MRI, which was highly significant compared with CT and conventional MRI. Overestimation for superficial tumors was high with CT (31.25%) and conventional MR imaging (25%), but was significantly reduced with dynamic MR imaging (8.3%). The percentages of underestimation in surgically proved invasive tumours (pT2- pT4) were lowest with dynamic MR imaging. CONCLUSION: CT and MR imaging are less accurate in the evaluation of the depth of mural invasion and for both techniques overstaging is the most frequent error. Dynamic contrast-enhanced MRI with 87% of accuracy, 8.3% overestimation for superficial tumours and lowest underestimation for invasive tumours, make this imaging considerably more accurate.	bladder
Minimally invasive establishment of murine orthotopic bladder xenografts.	Orthotopic bladder cancer xenografts are the gold standard to study molecular cellular manipulations and new therapeutic agents in vivo. Suitable cell lines are inoculated either by intravesical instillation (model of nonmuscle invasive growth) or intramural injection into the bladder wall (model of invasive growth). Both procedures are complex and highly time-consuming. Additionally, the superficial model has its shortcomings due to the lack of cell lines that are tumorigenic following instillation. Intramural injection, on the other hand, is marred by the invasiveness of the procedure and the associated morbidity for the host mouse. With these shortcomings in mind, we modified previous methods to develop a minimally invasive approach for creating orthotopic bladder cancer xenografts. Using ultrasound guidance we have successfully performed percutaneous inoculation of the bladder cancer cell lines UM-UC1, UM-UC3 and UM-UC13 into 50 athymic nude. We have been able to demonstrate that this approach is time efficient, precise and safe. With this technique, initially a space is created under the bladder mucosa with PBS, and tumor cells are then injected into this space in a second step. Tumor growth is monitored at regular intervals with bioluminescence imaging and ultrasound. The average tumor volumes increased steadily in in all but one of our 50 mice over the study period. In our institution, this novel approach, which allows bladder cancer xenograft inoculation in a minimally-invasive, rapid and highly precise way, has replaced the traditional model.	bladder
Alterations of global histone H3K9 and H3K27 methylation levels in bladder cancer.	BACKGROUND: Epigenetic alterations, including histone modifications, play an important role during carcinogenesis. This study was designed to systematically investigate histone H3K9 and H3K27 methylation levels in bladder cancer (BCa) tissue. METHODS: A tissue microarray with urothelial BCa (150 non-muscle-invasive BCa, NMIBC; 121 muscle-invasive BCa, MIBC; 31 metastatic BCa, MET) and normal urothelium (29, CTRL) specimen was used to determine the global levels of H3K9 and H3K27 mono-, di- and tri-methylation. RESULTS: Global levels of H3K9 and H3K27 methylation were significantly higher in CTRL than in BCa, and levels in NMIBC were higher compared to MIBC. Histone methylation levels of MET resembled MIBC. We observed furthermore a correlation of histone methylation levels with pT stage (H3K9me1, H3K9me2, H3K9me3, H3K27me1, H3K27me3) and grade (H3K9me2, H3K9me3, H3K27me1) in NMIBC. H3K9me1, H3K9me3, H3K27me1 and H3K27me3 levels were also correlated with pT stage in MIBC. Histone modifications were not associated with recurrence-free or cancer-specific survival. CONCLUSIONS: Global histone H3K9 and H3K27 methylation levels are altered in BCa.	bladder
A system-level pathway-phenotype association analysis using synthetic feature random forest.	As the cost of genome-wide genotyping decreases, the number of genome-wide association studies (GWAS) has increased considerably. However, the transition from GWAS findings to the underlying biology of various phenotypes remains challenging. As a result, due to its system-level interpretability, pathway analysis has become a popular tool for gaining insights on the underlying biology from high-throughput genetic association data. In pathway analyses, gene sets representing particular biological processes are tested for significant associations with a given phenotype. Most existing pathway analysis approaches rely on single-marker statistics and assume that pathways are independent of each other. As biological systems are driven by complex biomolecular interactions, embracing the complex relationships between single-nucleotide polymorphisms (SNPs) and pathways needs to be addressed. To incorporate the complexity of gene-gene interactions and pathway-pathway relationships, we propose a system-level pathway analysis approach, synthetic feature random forest (SF-RF), which is designed to detect pathway-phenotype associations without making assumptions about the relationships among SNPs or pathways. In our approach, the genotypes of SNPs in a particular pathway are aggregated into a synthetic feature representing that pathway via Random Forest (RF). Multiple synthetic features are analyzed using RF simultaneously and the significance of a synthetic feature indicates the significance of the corresponding pathway. We further complement SF-RF with pathway-based Statistical Epistasis Network (SEN) analysis that evaluates interactions among pathways. By investigating the pathway SEN, we hope to gain additional insights into the genetic mechanisms contributing to the pathway-phenotype association. We apply SF-RF to a population-based genetic study of bladder cancer and further investigate the mechanisms that help explain the pathway-phenotype associations using SEN. The bladder cancer associated pathways we found are both consistent with existing biological knowledge and reveal novel and plausible hypotheses for future biological validations.	bladder
Urological complications of illicit drug use.	Illicit drug use is prevalent worldwide; over 24 million people are estimated to have used recreational drugs during the past month in the UK and USA alone. Illicit drug use can result in a wide spectrum of potential medical complications that include many urological manifestations. To ensure optimal care and treatment, urologists need to be cognizant of these complications in their patients, particularly among youths. Ketamine uropathy is thought to affect over one-quarter of ketamine users and can lead to severe lower urinary tract symptoms, as well as upper tract obstruction. Cannabis use has been associated with an increased risk of bladder cancer, prostate cancer and nonseminomatous germ cell tumours in case-control studies. Fournier's gangrene has been reported following injection of heroin and cocaine into the penis. Excessive use of cough medicines can lead to the development of radiolucent stones composed of ephedrine, pseudoephedrine and guaifenesin. As the current evidence is mostly limited to case reports and case series, future epidemiological studies are needed to fully address this issue.	bladder
Resveratrol induces apoptosis of bladder cancer cells via miR‑21 regulation of the Akt/Bcl‑2 signaling pathway.	Resveratrol, an edible polyphenolic phytoalexin present in grapes and red wine, has been reported to inhibit proliferation and induce apoptosis of bladder cancer cells. In the present study, the molecular mechanisms of resveratrol on human bladder cancer cell apoptosis was examined. The effect of resveratrol on the viability and apoptosis of T24 and 5637 cells was measured using an MTT assay and flow cytometric analysis, respectively. Next, the effect of resveratrol on miR‑21 expression was detected by real‑time PCR. The expression of phospho‑Akt and Bcl‑2 following treatment with resveratrol or the downregulation of miR‑21 expression were also measured. Resveratrol induced the cytotoxicity and apoptosis of T24 and 5637 cells in a dose‑dependent manner. Resveratrol decreased the expression of miR‑21, the level of phospho‑Akt and Bcl‑2 protein expression. In addition, the downregulation of miR‑21 expression inhibited the level of phospho‑Akt and Bcl‑2 expression. Insulin‑like growth factor‑1 was able to reverse the effect of the miR‑21 inhibitor on Bcl‑2 expression and apoptosis in T24 and 5637 cells. Notably, overexpression of miR‑21 expression was able to restore the inhibition of Akt activity, downregulation of Bcl‑2 expression and apoptosis induced by resveratrol. Collectively, data revealed that the effect of resveratrol on bladder cancer cell apoptosis was due to miR‑21 regulation of the Akt/Bcl‑2 signaling pathway.	bladder
The role of pelvic lymphadenectomy in non-muscle invasive bladder cancer.	INTRODUCTION: We evaluated whether the extent of lymphadenectomy at the time of radical cystectomy for non-muscle invasive bladder cancer (NMIBC) impacts recurrence free survival. MATERIALS AND METHODS: We conducted an IRB approved retrospective analysis of patients with clinical NMIBC who underwent radical cystectomy from 1990-2010. Patients were stratified based on extent of lymph node dissection using total lymph node yield as a surrogate indicator of lymph node dissection extent, with cut off analyses performed at 0, 8, 10, and 20 nodes removed. Analyses of recurrence free survival (RFS) were performed using log-rank analysis and multivariate Cox regression. RESULTS: One hundred and ninety-six patients with NMIBC met the inclusion criteria for this study, with no differences in RFS detected in those who had ≥ 10 nodes compared to < 10 nodes removed (p = 0.63). Upon multivariate analysis, ≥ 10 nodes removed (HR 1.00; p = 0.99) was not significantly associated with decreased RFS, while high grade tumor (HR 3.22; p = 0.05) and positive margin status (HR 3.87; p = 0.04) were. The median number of nodes removed was 8 (range 0-45), with no difference in RFS using this as a cut off point (p = 0.19). The removal of ≥ 20 nodes did not predict worse survival compared to < 20 nodes removed (p = 0.07). CONCLUSIONS: Although the extent of lymphadenectomy has been associated with improved survival in patients undergoing radical cystectomy for muscle invasive bladder cancer, we were unable to detect an impact of lymph node dissection extent on RFS in patients with NMIBC. This finding emphasizes that when determining extent of lymph node dissection in radical cystectomy, one size does not fit all.	bladder